Known processes for asymmetrically synthesizing optically active ketones include (1) a process comprising asymmetric hydrogenation in the presence of a specific catalyst and (2) a process utilizing a hydrogenation reaction by the action of an enzyme.
In particular, known processes for preparing optically active ketones having a cyclopentanone or cyclohexanone skeleton include a process in which an .alpha.,.beta.-unsaturated ketone is asymmetrically hydrogenated by using, for example, a chiral ruthenium hydride complex containing trans-1,2-bis(diphenylphosphinomethyl)cyclobutane (hereinafter abbreviated as TBPC) (e.g., HRuCl(TBPC).sub.2, H.sub.2 Ru(TBPC).sub.2). For example, where an .alpha.,.beta.-unsaturated ketone as a substrate has a double bond subject to reduction in its ring (endo-form), isophorone (i.e., 3,5,5-trimethyl-2-cyclohexen-1-one), 3-methyl-2-cyclohexen-1-one, 2-methyl-2-cyclohexen-1-one, or 3-methyl-2-cyclopenten-1-one gives an optically active ketone having an optical purity of 62% ee, 22% ee, 26% ee, or 4.5% ee, respectively. Where a substrate has a double bond subject to reduction outside the ring thereof (exo-form), .alpha.-methylenetetralone (i.e., 3,4-dihydro-2-methylene-1-naphthalenone) gives an optically active ketone having an optical purity of 23% ee. Reference can be made to V. Massonneau, et al., Tetrahedron Letters, Vol. 27, (45), pp. 5497-5498 (1986).
An example of the process of using an enzyme is described in A. Kergomard, et al., J. Org. Chem., Vol. 47, pp. 792-798 (1982), in which 2-methyl-2-cyclohexen-1-one is reduced with Beauveria sulfurescens to obtain an optically active ketone having an R-configuration at the 2-position in a percent yield of 30%.
In the field of synthesis of pharmaceuticals, a process for synthesizing 11-deoxyprostaglandin E comprising asymmetrically reducing prostaglandin A as a typical .alpha.,.beta.-unsaturated cyclopentenone by using a microorganism is reported in U.S. Pat. No. 3,930,952.
Further, it has been proposed to biologically reduce oxoisophorone to obtain (4R,6R)-4-hydroxy-2,2,6-trimethyl-cyclohexanone which is an intermediate for synthesizing astaxanthin which is a kind of carotenoid, xanthine, or loliolide as described in R. Zell, et al., Helv. Chim. Acta, Vol. 59, p. 1832 (1976).
However, the conventional processes comprising asymmetric hydrogenation using a metal complex, e.g., HRuCl(TBPC).sub.2, as a catalyst find difficulty in obtaining an optically active ketone having a satisfactorily high optical purity.
In the case of the processes using an enzyme, on the other hand, the steric configuration of a product obtained is limited in many cases. In addition, these processes involve complicated procedures for separating the product from microbial cells.
It has been therefore demanded to develop a process for effectively obtaining an optically active ketone with a high optical purity.